E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SARS-CoV-2 infection (COVID-19) |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084268 |
E.1.2 | Term | COVID-19 |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To characterize the dynamics of viral clearance (incl. viral cultures, qPCR) following ensovibep administration • To evaluate the serum pharmacokinetics of single, i.v. doses of ensovibep in patients with symptomatic COVID-19 disease
|
|
E.2.2 | Secondary objectives of the trial |
• To observe the evolution of clinical symptoms for COVID-19 following ensovibep administration • To characterize the tolerability of two single i.v. flat dose levels of ensovibep in patients with symptomatic COVID-19 disease
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men or non-pregnant women, between 18 and 70 years on the day of inclusion. 2. Presence of one or more mild or moderate COVID-19 symptoms: Fever, cough, sore throat, malaise, fatigue, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion. 3. Positive test for SARS-CoV-2 in upper respiratory swab on the day of dosing (rapid antigen test). 4. Female subjects must agree to use highly effective contraception as described in section 4.5.1 or must be of non-childbearing potential. A woman is considered to be of non-childbearing potential if she meets one of the following criteria: a. be post-menopausal (spontaneous amenorrhea for at least 12 months,); or b. has no uterus, ovaries or fallopian tubes. 5. Agree to follow the contraception requirements of the trial as described in section 4.5.1. 6. Understand and agree to comply with planned study procedures, including nasopharyngeal swabs and venous blood samples. 7. Able to communicate well with the investigator in the Dutch language and has provided signed informed consent.
|
|
E.4 | Principal exclusion criteria |
1. Requiring hospitalization at time of screening, or at time of study drug administration. 2. Oxygen saturation (SpO2) ≤ 93 percent (%) on room air at sea level, respiratory rate ≥ 30 per minute, or heart rate ≥125 per minute. 3. Known allergies to any of the components used in the i.v. formulation of ensovibep. 4. Any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study. 5. Any co-morbidity requiring hospitalization or surgery within <7 days, or that is considered life-threatening within 29 days. 6. A patient reported history (prior to the current episode) of a positive SARS-CoV-2 serology test or a history of PCR confirmed SARS-CoV-2 infection. 7. Prior or concurrent use of SARS-CoV-2 antiviral medication, including convalescent serum or anti-viral antibodies. 8. Concurrent enrollment in any other type of medical research for improving COVID-19 outcomes or that is judged by the investigator not to be scientifically or medically compatible with this study. 9. Women that are currently breast feeding, pregnant, or plan to get pregnant during the duration of the trial. 10. Severe immunocompromised status (primary immunodeficiency, supraphysiological dose of systemic corticosteroids, transplant patients, known untreated HIV and CD4 T-cells <200/microliter) or use of any immunosuppressants that, in the opinion of the investigator, should preclude participation in this study. 11. Subjects at high risk for of COVID-19 related complications or mortality, defined as: a. Age 50 to 70 years and at least one of the following other risk factors: i. BMI >35 kg/m2 ii. Chronic Cardiac or pulmonary disease (e.g. atrial fibrillation, CAD, heart failure, COPD, asthma), that might pose additional risks in study participation, as per investigator decision iii. Ongoing clinically significant neurological disease (e.g. stroke or any other chronic debilitating neurological disease) iv. Chronic kidney disease with GFR <60 ml/min, as per medical history v. Rheumatic disease (e.g. rheumatoid arthritis, Systemic lupus erythematosus, psoriatic arthritis) vi. Cancer not in complete remission for >1 year (excluding baso -or spinocellular skin cancers) vii. Chronic liver disease (liver cirrhosis Child Pugh A/B/C or other disease leading to liver dysfunction) as per medical history b. Age < 50 years with 3 or more of the above-mentioned risk factors.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Changes from baseline to each time point of measurement in viral load (quantitative PCR) and viral cultures, as per assessment schedule • Duration in days to PCR negativity • Measurement of ensovibep in serum and assess PK paramenters (including Cmax, T1/2, Tmax, AUCinf, AUClast, CL, Vss)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Changes in the Assessment of 14 Common COVID-19-Related Symptoms score per the assessment schedule • Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit • Adverse events of special interest (AESIs) • Infusion-related reactions (IRRs) • Concomitant medication throughout the study at every study visit • Vital signs (pulse rate (bpm), systolic blood pressure (mmHg), diastolic blood pressure (mmHg), respiratory rate, temperature (ºC), and oxygen saturation (%)) as per the assessment schedule • Clinical laboratory tests (hematology and blood chemistry) as per the assessment schedule • Physical examinations (symptom directed) at every study visit • Assessment of local tolerability at injection site (Visual Infusion Phlebitis score)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |